G. S. Skinner, et al. first reported the condensation of 1,4-dihalo-2-butene and diethyl malonate in J. Am. Chem. Soc., 72, 1648(1950). The condensation was conducted under anhydrous conditions by reacting the dihalide with the pre-formed disodio anion of the malonic ester in an attempt to synthesize spirocyclopentane-1,5-barbiturates. Kierstead, et al. (J. Chem. Soc., 1952, 3610-21 and J. Chem. Soc., 1953, 1799) reported the preparation of diethyl 2-vinylcyclopropane-1,1-dicarboxylate by the condensation of 1,4-dibromo-2-butene and ethyl sodiomalonate and observed that continual attack by malonate and anion on the 2-vinylcyclopropane derivative produced side products, one of which was 2-vinylbutane-1,1,4,4-tetracarboxylate. Kierstead, et al. also extended the general reaction to ethyl cyanoacetate and ethyl acetoacetate to obtain the corresponding 2-vinylcyclopropane derivatives. In an attempt to develop a new synthetic route for the preparation of the cyclopentane counterparts by deoxyribonucleosides, Murdock, et al. in J. Amer. Chem. Soc., 27, 2395 (1962) reported condensing cis-1,4-dichlorobutene-2 with sodiomalonic ester under anhydrous conditions as the first step in their reaction sequence.
With all of the above reactions, as well as in other reports dealing with the condensation of malonic esters with 1,4-dihalo-2-butenes, e.g. Birch, et al., J. Org. Chem. 23, 1390 (1958); Schmid, et al., J. Org. Chem. 32, 254 (1967); Stewart, et al., J. Org. Chem., 34, 8 (1969), the metal alkoxide and malonic ester were prereacted to first form the corresponding sodiomalonate anion, which was then very slowly added to the dihalobutene. This procedure was considered essential for the successful conduct of the reaction and to optimize the yield of the vinylcyclopropane dicarboxylate. The dihalo compound was not combined directly with the alcoholic caustic to avoid ether by-product formation since this is a well known and widely used procedure (Williamson synthesis) for the preparation of ethers. By adding the malonate anion to the dihalobutene and carefully controlling the rate of this addition, it was believed that linear diaddition products formed by either continued attack on the vinylcyclopropane product by malonate anion or reaction of both the halogens on a single molecule would be minimized. Strictly anhydrous conditions were employed throughout the entire reaction procedure, i.e. during the formation of the anion and the addition of the anion to the dihalobutene, since it is generally accepted that for malonate and acetoacetic ester condensations the presence of water is detrimental (Practical Organic Chemistry, A. I. Vogel, 3rd Ed., Longmans, Green and Co., Ltd., London (1967) pp. 481-486). Even as late as 1970 the classical procedure first developed by Skinner and coworkers was still being used as evidenced by the report of Den Besten, et al. (J. Chem. Eng. Data, 15, 453 (1970)) who prepared diethyl 2-vinylcyclopropane-1,1-dicarboxylate for subsequent thermal decomposition.
In view of the complex state of the reagents, the requirement to operate under strictly anhydrous conditions and the necessity for a sophisticated reaction vessel to carry out the detailed addition, it has heretofore not been practical to prepare vinylcyclopropane derivatives on a commercial scale via such condensation reactions.
U.S. Pat. Nos. 4,328,168 and 4,328,169 inter alia, describe improved processes for the preparation of vinylcyclopropane derivatives. These processes are adaptable to commercial operation and involve reacting, in a fluid state, an alkylating agent, e.g. 1,4-dichlorobutene-2, and an activated methylene compound, e.g. dimethyl malonate, in the presence, respectively, of a cyclic polyether compound or an alkylene oxide derivative and an alkali metal compound. A wide variety of cyclopropane derivatives are readily obtained by these processes.
Another process which has met with favor in overcoming the disadvantages of the earlier literature processes is the phase-transfer-catalyzed synthesis of vinylcyclopropane derivatives described in U.S. Pat. No. 4,252,739, among others, and which involves reacting an alkylating agent, e.g. 1-4-dichlorobutene-2, and an activated methylene compound, e.g. a lower alkyl malonate in the presence of an onium compound, an alkali metal compound and water. While this process works well with certain lower alkyl esters of 2-vinylcyclopropane-1,1-dicarboxylate, for example the ethyl and higher esters, it produces lower yields of the order of &lt;10% when dimethyl 2-vinylcyclopropane-1,1-dicarboxylate is sought to be obtained. It appears that the phase-transfer process when directed to the synthesis of the dimethyl ester produces low yields due to ester saponification which is apparently competitive with the condensation reaction in the presence of methyl esters but which saponification is insignificant with the ethyl and higher esters.
It would be highly desirable, therefore, if an improved process for the preparation of di lower alkyl 2-vinylcyclopropane-1,1-dicarboxylates by the reaction of 1,4-dihalobutenes and malonic esters were available which did not possess the drawbacks of the prior art processes. It would also be desirable if it were possible to eliminate the need for conducting the process in a stepwise manner, i.e., preforming the anion, and if the need for maintaining strictly anhydrous conditions could be eliminated and if the yield of the desired product could be increaseed, the process would have even greater utility. These and other advantages are realized by the improved process of this invention.
It is, therefore, an object of the present invention to provide an improved process for the production of di lower alkyl-2-vinylcyclopropane-1,1-dicarboxylates by the reaction of 1,4-dihalobutenes and malonic esters which does not have the drawbacks associated with the prior art processes.
It is a further object of the present invention to provide a process of preparing high yields of dimethyl 2-vinylcyclopropane-1,1-dicarboxylate without the attendant saponification of the ester with resulting low yields of the desired product as has been observed in the prior art processes.
These and other objects of the present invention are readily achieved by the novel process hereinafter described.